THE NEW ARMS RACE:

1

• THE NEW ARMS RACE
• Making the Case for a Comprehensive International
  Compact for Infectious Diseases
• Harvey Rubin, MD, PhD
• Infectious Disease Society of America
• Toronto, October 12, 2006

2
The problem
Recognizing the impact of infectious diseases on
national and international health, economic
development and security, can a truly
comprehensive agreement between states be
developed that will limit and control known,
newly discovered or deliberately created
infectious diseases?
3
The need is well documented

• Emerging Infections Microbial Threats to Health
  in the United States 1992, 2003, Institute of
  Medicine
• The Global Infectious Disease Threat and Its
  Implications for the United States 2000,
  unclassified report from the National
  Intelligence Council
• The Darker Bioweapons Future 2003, unclassified
  CIA document analyzed the many benefits of modern
  molecular biology weighed against the danger that
  the effects of engineered biological agents
  could be worse than any disease known to man.
• National Security Strategy 2006, Public health
  challenges like pandemics (HIV/AIDS, avian
  influenza) ... recognize no borders. The risks to
  social order are so great that traditional public
  health approaches may be inadequate,
  necessitating new strategies and responses. ...
  (italics added). 

4
Dangerous assumption that an agreement exists
5

Human Rights 1. International Covenant on
Economic, Social and Cultural Rights (New York,
1966) 2. International Covenant on Civil and
Political Rights (New York, 1966) 3. Optional
Protocol to the International Covenant on Civil
and Political Rights (New York, 1966) 4.
Convention on the Prevention and Punishment of
the Crime of Genocide (New York, 1948) 5.
Convention against Torture and Other Cruel,
Inhuman or Degrading Treatment or Punishment (New
York, 1984) 6. Optional Protocol to the
Convention against Torture and Other Cruel,
Inhuman or Degrading Treatment or Punishment (New
York, 2002) 7. International Convention on the
Protection of the Rights of All Migrant Workers
and Members of their Families (New York, 1990)
8. Optional Protocol to the Convention on the
Rights of the Child on the involvement
of children in armed conflict (New York, 2000) 9.
Optional Protocol to the Convention on the Rights
of the Child on the sale of children, child
prostitution and child pornography (New York,
2000)
6
Refugees 10. Convention Relating to the Status of
Refugees (Geneva, 1951) 11. Protocol Relating to
the Status of Refugees (New York, 1967) Penal
Matters 12. Rome Statute of the International
Criminal Court (Rome, 1998) 13. Agreement on the
Privileges and Immunities of the International
Criminal Court (New York, 2002) 14. Convention on
the Safety of United Nations and Associated
Personnel (New York, 1994) Terrorism 15.
International Convention for the Suppression of
Terrorist Bombings (New York, 1997) 16.
International Convention for the Suppression of
the Financing of Terrorism (New York,1999) 17.
International Convention for the Suppression of
Acts of Nuclear Terrorism (New York, 2005)
7
Organized Crime and Corruption 18. United Nations
Convention against Transnational Organized Crime
(New York, 2000) 19. Protocol to Prevent,
Suppress and Punish Trafficking in Persons,
Especially Women and Children, supplementing the
United Nations Convention against
Transnational Organized Crime (New York,
2000) 20. Protocol against the Smuggling of
Migrants by Land, Sea and Air, supplementing
the United Nations Convention against
Transnational Organized Crime (New York,
2000) 21. Protocol against the Illicit
Manufacturing of and Trafficking in Firearms,
Their Parts and Components and Ammunition,
supplementing the United Nations
Convention against Transnational Organized Crime
(New York, 2001) 22. United Nations Convention
against Corruption (New York, 2003)
8
Environment 23. Kyoto Protocol to the United
Nations Framework Convention on Climate
Change (Kyoto, 1997) 24. Rotterdam Convention on
the Prior Informed Consent Procedure for
Certain Hazardous Chemicals and Pesticides in
International Trade (Rotterdam, 1998) 25.
Stockholm Convention on Persistent Organic
Pollutants (Stockholm, 2001) 26. Cartagena
Protocol on Biosafety to the Convention on
Biological Diversity (Montreal, 2000) Law of the
Sea 27. United Nations Convention on the Law of
the Sea (Montego Bay, 1982) and Agreement
relating to the implementation of Part XI of the
United Nations Convention on the Law of the Sea
of 10 December 1982 (New York, 1994)
9
Disarmament 28. Comprehensive Nuclear-Test-Ban
Treaty (New York, 1996) 29. Convention on the
Prohibition of the Use, Stockpiling, Production
and Transfer of Anti-Personnel Mines and on their
Destruction (Oslo, 1997) Law of Treaties 30.
Vienna Convention on the Law of Treaties (Vienna,
1969) Health 31. WHO Framework Convention on
Tobacco Control (Geneva, 21 May 2003)
10

• BUT NO COMPREHENSIVE PROGRAM FOR INFECTIOUS
  DISEASES

11
What about the

• International Health Regulations (IHR) of the
  World Health Organization?
• The Biological Weapons Convention (BWC)?

12
THE SOLUTION
We propose a comprehensive four-part
International Compact for Infectious Diseases
(the Compact)
13
Treaties and Compacts organizational benefits
and drawbacks

• Compact Benefits
• Quick to set up and provides a framework for
  action.
• Brings together a broad coalition of partners
  around a central issue.
• Promotes voluntary compliance of laboratories,
  companies, etc.
• Compact Drawbacks
• Enforcement relies on soft power and voluntary
  compliance.
• Soft power may prove ineffective during a health
  crisis.

• Treaty Benefits
• Provides an international legal basis for
  enforcement.
• Creates a body of durable hard law around an
  issue.
• Draws on the power of governments to regulate
  and license within their jurisdiction
• Treaty Drawbacks
• Ratification is slow and may limit action on
  urgent issues.
• States may perceive enforcement clauses as an
  unacceptable burden.

14
A Two-Pronged Approach

• Eligible Parties States
• Method of Participation Ratification

Eligible Members NGOs, academic institutions,
corporations, independent research labs Method
of Participation Pledge of Membership and
Voluntary Compliance
15
Treaty and Compact complementary systems

• By providing parallel frameworks for different
  parties, the overall project will, over time,
  achieve the benefits of each.
• Domestic partners who are signatories to the
  compact will pressure states to comply with the
  treaty.
• Legitimacy and understanding of the overall
  system will be promoted through involvement of
  both state and non-state actors

16
Compacts are effective governance structures

• 1) Human Rights
• Inter-American Declaration of Human Rights
  (Organization of American States)
• Helsinki Accords (Organization of Security and
  Cooperation in Europe)
• Labor Rights Laws (International Labor
  Organization)
• Sullivan Principles on Apartheid (Private Sector
  Active in South Africa)
• McBride Principles (Private Sector Active in
  Northern Ireland)
• 2) Environment
• Prior Informed Consent for Hazardous Chemicals in
  International Trade
• Driftnet Fishing (UN General Assembly Series of
  Resolutions 1989-1992)
• Antarctica Treaty Recommended Measures
• Convention on Migratory Species (States were
  encouraged to create informal agreements within
  the treaty Memorandums of Understanding)
• 3) Arms Control/Disarmament
• Nuclear Safety Measures (The International Atomic
  Energy Agency)
• Suppliers Export Controls (Dual Use Technologies)
  
• Landmines (Before the Ottawa Treaty)
• 4) Trade/Finance
• Money Laundering (World Bank)
• Standards Harmonization (International Standards
  Organization)
• Environmental Soft Law Linkages with Trade (Asian
  Pacific Economic Community)

17
The Compact Part 1

• Establish, maintain and monitor international
  standards for surveillance and reporting of
  infectious diseases using advanced information
  technology to ensure timeliness, interoperability
  and security

18
The Compact Part 2

• Establish, maintain and monitor international
  standards for best laboratory practices

19
The Compact Part 3

• Expand capabilities for the production of
  vaccines and therapeutics expressly for emerging
  and reemerging infections

20
The Compact Part 4

• Establish, maintain and monitor a network of
  international research centers for microbial
  threats.

21
Part 1Establish, maintain and monitor
international standards for surveillance and
reporting of infectious diseases

• States parties to the Compact would set up
  standard, secure computer architectures for
  biosurveillance information systems
• Parties would define, and continuously refine,
  criteria for surveillance and reportable agents
  using latest information on endemic and emerging
  naturally occurring pathogens

22

• Epidemic and Pandemic Alert and Response
• Epidemics and pandemics can place sudden and
  intense demands on health systems. They expose
  existing weaknesses in these systems and, in
  addition to their morbidity and mortality, can
  disrupt economic activity and development.
• The world requires a global system that can
  rapidly identify and contain public health
  emergencies and reduce unneeded panic and
  disruption of trade, travel and society in
  general.
• The revised International Health Regulations,
  IHR(2005) provide a global framework to address
  these needs through a collective approach to the
  prevention, detection, and timely response to any
  public health emergency of international concern.

23
Epidemic and Pandemic Alert and Response (EPR)
has six core functions

• Support Member States for the implementation of
  national capacities for epidemic preparedness and
  response in the context of the IHR(2005),
  including laboratory capacities and early warning
  alert and response systems
• Support national and international training
  programmes for epidemic preparedness and response
  
• Coordinate and support Member States for pandemic
  and seasonal influenza preparedness and response
• Develop standardized approaches for readiness and
  response to major epidemic-prone diseases (e.g.
  meningitis, yellow fever, plague)
• Strengthen biosafety, biosecurity and readiness
  for outbreaks of dangerous and emerging pathogens
  outbreaks (e.g. SARS, viral haemorrhagic fevers)
• Maintain and further develop a global operational
  platform to support outbreak response and support
  regional offices in implementation at regional
  level.

24
From International Sanitary Conventions to
Global Health Security The New International
Health Regulations David P. Fidler Chinese
Journal of International Law (2005), Vol. 4, No.
2, 325392
25
IHR issues

• no mechanism for dispute settlement or
  enforcement
• fundamental financial burden falls on developed
  states, not developing nations
• IHRs do not increase access to therapeutics nor
  stimulate vaccine development

From International Sanitary Conventions to Global
Health Security The New International Health
Regulations David P. Fidler Chinese Journal of
International Law (2005), 4, 325392
26
Challenges for any surveillance and reporting
system

• trust between signatory nations and a willingness
  to share biosurveillance data
• developing incentives to share data
• creation of a common architecture for information
  systems requires common ontologies
• developing and validating new algorithms and
  models of disease spread
• consequences of non-reporting, or significantly
  under-reporting the incidence of communicable
  diseases

27
Technical solutions

• integrate current initiatives into a national
  health IT strategy and federal architecture to
  reduce the risk of duplicative efforts
• develop and adopt consistent interoperability
  standards
• create enough flexibility to bring together
  disparate underlying IT languages and
  technologies to provide a common operating
  picture
• generate the ability to accept multiple data
  formats used by agencies that provide the
  bio-surveillance information

28
Technical solutions

• generate the ability to feed information back to
  the originating agencies providing
  bio-surveillance information in a format each
  agency can accept
• identify data flows that will evolve during the
  developmental process
• allow the methods of analysis to evolve and adapt
  as new data become available or existing data
  sets are improved
• know and evaluate the effectiveness of the
  current underlying algorithms, methods, and
  structures for biosurveillance data analysis.

29
Governance solutions

• The Compact will use soft methods to encourage
  reporting and discourage non-compliance
• Compliance status will be made public
• Parties not reporting or under-reporting disease
  incidence will have lower priority to
• vaccines and therapeutics
• research done through the Compact

30
Part 2 International Standards for Best
Laboratory Practices

• Bio-safety at risk
• Laboratory personnel
• Local public health
• National and international public health
• Unavaoidable linkage to bio-security

31
Example of International Standards for Best
Laboratory Practices

• Survey of 300 Asian life scientists engaged in
  research with over 60 different infectious agents
  and/or toxins.
• 1. examine the policies and standards employed to
  advance biosafety and biosecurity
• 2. understand the practices, equipment and
  facilities used by these researchers
• 3. examine existing regulations in the context of
  the infectious pathogens they study
• 4. identify and address gaps in the development
  and implementation of policies related to
  laboratory biosafety and biosecurity

32
Results of the Sandia survey

• Most of the laboratories profiled in the study
  perform risk assessments as the antecedent to
  instituting a biosafety plan.
• These plans, along with a laboratorys
  biosecurity practices are highly influenced by
  each countrys national government.
• Five of the top nine infectious agents identified
  by respondents should be studied under biosafety
  level (BSL) 3 conditions, however almost
  two-thirds of researchers state they are working
  only with BSL 2 practices.

33
Another example of best practices recent
publication of 1918 Pandemic Influenza Virus
Papers
The 1918 virus and recombinant H1N1 influenza
viruses were generated using the previously
described reverse genetics system (8, 14). All
viruses containing one or more gene segments from
the 1918 influenza virus were generated and
handled under high-containment biosafety level 3
enhanced (BSL3) laboratory conditions in
accordance with guidelines of the National
Institutes of Health and the Centers for Disease
Control and Prevention (15).
34
1918 Flu and Responsible Science
I firmly believe that allowing the publication
of this information was the correct decision in
terms of both national security and public
health.
Science Editorial Vol. 310, 7 October 2005
Philip A. Sharp
35
The 1918 flu genome Recipe for Destruction
This is extremely foolish. The genome is
essentially the design of a weapon of mass
destruction.
New York Times Op-Ed October 17, 2005 Ray
Kurzweil and Bill Joy contributors
36
Best Lab Practices Model

• 1. The Compact develops and adopts best
  laboratory practices with input from signatories.
• 2. Signatories set up internal certification
  bodies responsible for ensuring compliance with
  BLPs.
• 3. Signatories submit annual reports to expert
  panel within Compact verifying compliance with
  BLPs.
• 4. Signatories that do not comply with BLPs
  suffer reduced access to compact institutions and
  data, and their non-compliance in publicized.

37
Part 3 Expansion of capabilities for the
production of vaccines and therapeutics expressly
for emerging and reemerging infections

• An innovative solution for the limited base of
  manufacturing and distribution of therapeutics
  and vaccines has to be achieved
• Government as well as large, multi-national
  pharmaceutical concerns and the biotechnology
  industry need to engage in a commitment to expand
  the manufacturing base
• Manufacturing contracts would be awarded to the
  countries or organizations with the most
  compelling offer, including commitments to
  assurance of continuity of supply and operations,
  safety, security and infrastructure.
• The signatories to the Compact would agree to
  fund the efforts sufficiently, perhaps
  representing a percentage of their GDP, thereby
  pooling the resources of many nations to create
  assured supplies of drugs and vaccines on a
  global scale as well as for specific local use.

38
Challenges

• The market for therapeutics and vaccines in the
  developing world is too small to attract serious
  commercial research investment
• Even in the developed world, vaccine markets
  generally suffer from high up-front costs
  relating to research and regulation, and
  uncertain demand over time
• Vaccines against potential biological weapons
  will suffer from high demand uncertainties and,
  should a bioterror event occur, may be
  requisitioned rather than purchased at market
  price
• The enterprise requires high levels of
  transparency, oversight and acceptance of
  international standards for licensure
• Incentives and enforcement must be considered

39
Editorial September 6, 2006

• Vaccine Futures
• One of the big reasons that companies dont try
  to develop vaccinations for poor-country diseases
  is that they fear there wont be a market for
  them. So what if rich countries promised to buy
  them?
• Thats the very simple idea behind a new plan to
  entice companies into making vaccines for
  illnesses that mostly kill poor people, like
  malaria and tuberculosis. The program will be
  discussed by finance officials from wealthy
  nations at a meeting in Rome tomorrow. It works
  like this Rich countries commit to pay a
  specific amount to help poor countries buy a
  guaranteed supply of a needed, effective vaccine.
  The subsidy would allow the manufacturer to
  recoup its investment and earn a profit. The
  company agrees that after it has received the
  pledged amount, it will sell to poor countries
  cheaply.
• A panel of experts recommended that the idea be
  tried first to promote a vaccine against
  pneumococcal disease, which kills about 1.6
  million people a year, making it the leading
  vaccine-preventable cause of death. AIDS is
  making this kind of infection more common, and
  the bacteria are increasingly resistant to the
  antibiotics used to treat them.
• In the last few years, researchers have tried
  several novel financing ideas. Many combine
  government and charitable financing with
  industrial know-how. This idea would complement
  the others. The Bush administration has been
  reluctant to join international financing
  mechanisms. But it has no reason not to jump on
  this plan, which will benefit American companies
  and is a private-sector, market-driven program
  that pays only for success.

40
Potential Financial Models

• 1. Advance Market Commitments
• 2. International Finance Facility for
  Immunization (IFFIm)- bond mechanism to pay for
  vaccines borrowing operating funds in the
  international capital markets over 10 years,
  expecting a triple-A credit rating
• 3. International drug purchase facility (IDPF)
  French plan to levy tax on airline tickets

41
Among the many benefits

• The Compact equitably spreads the high cost of
  manufacturing and distribution of drugs and
  vaccines across a group of nations.
• It creates a structure with which to develop
  incentives for large pharmaceutical corporations
  to undertake the development of vaccines and
  therapeutics.
• It provides the mechanism to achieve the common
  goal of providing the world with standardized and
  authenticated agents.
• It will address the legal issues of international
  pharmaceutical licensing.

42
Part 4Establishment, maintenance and monitoring
of a network of international research centers
for microbial threats.

• The research centers should have a permanent
  faculty and staff as well as visiting fellowships
  and studentships.
• The lasting positive impacts of international
  research centers include fostering long-term
  relationships between scientists, establishing a
  culture of research responsibility and serving as
  the nucleus for safe applications of
  interdisciplinary sciences globally.
• The example of the "Rice Institutes" funded by
  the Rockefeller Foundation for fifteen years and
  sustained by the Consultative Group in
  International Agricultural Research, provides an
  example.
• RICE BIOTECHNOLOGY Rockefeller to End Network
  After 15 Years of Success. Dennis Normile
  Science 19 Nov. 1999286, 1468 1469

43
The Compact incentives and enforcements

• These recommendations are made with full
  awareness of the inherent legal, political,
  diplomatic and economic challenges of
  multilateral compacts. 
• We believe that a major strength of linking the
  production and distribution of therapeutics and
  vaccines with biosafety, biosecurity and improved
  access to and participation in research programs
  creates a global incentive of compassion,
  maximization of human health and welfare and
  economic and scientific development.
• Furthermore, the Compact uses both incentives and
  penalties to create a cohesive international body
  that does not challenge sovereignty, but pools
  resources.
• Non-participation by any given state would lower
  its priority to receive the cost benefits of
  therapeutics and vaccines.
• The non-participating state would have lower
  priority in the research center.

44
Benefits the whole is greater than the sum of
its parts

• 1. Provide access to specific therapeutics and
  vaccines that are relevant to the signatories.
• 2. Provide access to cheaper and more highly
  standardized therapeutics and vaccines.
• 3. Ensure better quality control of vaccines,
  therapeutics and diagnostics in the developing
  world, leading to fewer expired or counterfeit
  agents.
• 4. Provide access to and participation in
  high-level research.
• 5. Provide developing and developed states with a
  voice in the direction of research and
  development.

45
Benefits the whole is greater than the sum of
its parts

• 6. Distribute the costs and risks of research and
  development across a number of countries
• 7. Provide more complete datasets on emerging
  infections and potential pandemics.
• 8. Create a more competitive market for vaccine
  and therapeutic development targeting diseases of
  relevance to signatory nations.
• 9. Enhance and enable human health and well
  being, economic development, and basic biological
  research.

46
Global Collaborators

• Martin J. Blaser, M.D., Frederick H. King
  Professor of Internal Medicine, Chair, Department
  of Medicine, Professor of Microbiology, New York
  University School of Medicine
• William W. Burke-White, Assistant Professor of
  Law, University of Pennsylvania, Member,
  Government of Rwanda, Constitutional Commission,
  Member, International Criminal Tribunal for
  Yugoslavia, The Hague.
• Arturo Casadevall, MD, PhD. Professor, Medicine,
  Microbiology, Immunology, Chair, Department of
  Microbiology Immunology, Leo and Julia
  Forchheimer Professor of Microbiology
  Immunology
• Abdallah S. Daar D.PHIL(OXON), FRCP(LON),
  FRCS(ENG.ED.), FRCSC, FRS(C). Professor of
  Public Health Sciences and of Surgery at the
  University of Toronto, Director of the Program in
  Applied Ethics and Biotechnology, co-Director of
  the Canadian Program on Genomics and Global
  Health and Director of Ethics and Policy at the
  McLaughlin Centre for Molecular Medicine.
• David Franz, DVM. PhD, Senior Biological
  Scientist, Midwest Research Institute and
  Director of the National Agricultural Biosecurity
  Center at Kansas State University
• Sir Lawrence Freedman, Professor of War Studies
  and Vice Principal (Research), King's College
  London
• Malcolm Gillis, PhD. Zingler Professor of
  Economics and University Professor, Rice
  University
• Manfred S Green MD, PhD. Director, Israel Center
  for Disease Control , Professor of Epidemiology
  and Preventive Medicine in the Sackler Faculty of
  Medicine at Tel Aviv University Dr. Greens
  views do not necessarily reflect the views of the
  Israel Ministry of Health.

47

• Phillip A. Griffiths, PhD. Professor, School of
  Mathematics, Institute for Advanced Study,
  Princeton NJ. Former Director, Institute for
  Advanced Study, Princeton.
• J. Tomas Hexner, MBA. Director Science Initiative
  Group. Cambridge, Massachusetts
• Chung W. Kim, PhD. Director Emeritus, Korea
  Institute for Advanced Studies, Emeritus
  Professor, Physics and Astronomy, Johns Hopkins
  University
• Stuart B. Levy M.D., Professor of Molecular
  Biology and Microbiology and of Medicine and the
  Director of the Center for Adaptation Genetics
  and Drug Resistance at Tufts University, School
  of Medicine, Boston, Massachusetts
• Dr. Adel Mahmoud M.D. PhD., President of Merck
  Vaccines (retired).
• Erwann Michel-Kerjan, PhD., Managing Director of
  the Risk Management and Decision Processes Center
  at the Wharton School, University of Pennsylvania
• Peter A. Singer, MD, MPH, FRCPC , Co-Director
  of the Canadian Program in Genomics and Global
  Health Senior Scientist at the McLaughlin Centre
  for Molecular Medicine Professor of Medicine at
  University of Toronto and University Health
  Network and a Distinguished Investigator of the
  Canadian Institutes of Health Research.

48
Next steps

• Complete the legal, business and research cases
  by engaging
• the pharmaceutical industry
• the information technology industry
• NGOs
• Academia
• 2. Feedback and suggestions from you, log on to
• www.istar.upenn.edu/compact
• 3. Present plans to the appropriate national and
  international government agencies

49
(No Transcript)
50
Thanks to the University of Pennsylvania students

• Adrian Arroyo
• Dr. Jian Shin Teh
• Joanna Johnston
• Daniel Milich
• Jon Stott

51

• We choose to go to the moon in this decade and
  do the other things, not because they are easy,
  but because they are hard, because that goal will
  serve to organize and measure the best of our
  energies and skills, because that challenge is
  one that we are willing to accept, one we are
  unwilling to postpone, and one which we intend to
  win
• John F. Kennedy Rice University September 12,
  1962